The aims are to investigate the rheological behavior of red cell membranes (RCM), to study the interactions of RCM with the environment, to correlate these functions with the molecular organization of RCM, andto evaluate the role of RCM properties in circulatory regulation, in health and in disease. Rheology of RCM during deformation at constant area and during area stretching is studied on intact cells and on monolayers prepared from RCM components (new Project F), and modeled by theoretical computation. In the supplemental proposal, a similar approach will be used to study the rheology of leukocytes. The rheological data are correlated with the ultrastructure of RCM, with the microviscosity of RCM probed by fluorescence polarization, and with the molecular organization and function of specific membrane components. RCM proteins are examined by covalent labeling, and protein-lipid interactions will be explored by surface chemical and other techniques. The multidisciplinary approach is used to study: changes in RCM during cyclic deoxygenation of sickle cells; the relation of I-i antigens on sickle cell exoface to intracellular Hb F; properties of hexose receptor transport protein; electrochemical forces involved in interactions of RCM exoface with macromolecules; and the micromechanics of cell aggregation. The role of blood cell membrane properties in affecting flow dynamics and metabolic transport will be studied in the macro- and microcirculation (New Project G). Supplemental funds are requested for renovation, for meeting new needs in existing projects, and for adding new projects. The additional support will facilitate greatly our progress toward the ultimate goal of providing the fundamental knowledge needed to improve diagnosis and treatment of cardiovascular and blood diseases.